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Pulmonary clearance

Kuan-Lun Li, Yen-Chang Lin
The particle matter with diameter less 2.5μm (PM2.5) easier to adsorb toxic substance, and interfere with pulmonary gas exchange. In this study, cardioprotective effects of low molecular weight (LMW) fucoidan in cardiac hypertrophy subjects induced by PM2.5 exposure was conducted by measuring QT interval, Blood pressure, cardiac structure, metabolites and proteins expression in different organs. After PM2.5 exposure, increase in blood pressure, abnormal cardiac function (Prolongation of Action Potential Duration and QT Interval), and structral remodeling (cardiac hypertrophy and fibrosis) were recorded...
July 20, 2018: Oncotarget
William M Coutinho, Paulo J C Vieira, Fernanda M Kutchak, Alexandre S Dias, Marcelo M Rieder, Luiz Alberto Forgiarini
Context: Cough assist (CA) is a device to improve bronchial hygiene of patients with secretion in the airways and ineffective cough. Aims: To compare the physiological effects and the volume of secretion of mechanical insufflation-exsufflation (CA device) with isolated endotracheal suctioning in mechanically ventilated patients. Settings and Design: Randomized crossover trial. Materials and Methods: The patients were randomly allocated to the first technique, then the following technique was performed in the next day...
July 2018: Indian Journal of Critical Care Medicine
Helena M Izquierdo, Paola Brandi, Manuel-José Gómez, Ruth Conde-Garrosa, Elena Priego, Michel Enamorado, Sarai Martínez-Cano, Iria Sánchez, Laura Conejero, Daniel Jimenez-Carretero, Silvia Martín-Puig, Martin Guilliams, David Sancho
The rapid transit from hypoxia to normoxia in the lung that follows the first breath in newborn mice coincides with alveolar macrophage (AM) differentiation. However, whether sensing of oxygen affects AM maturation and function has not been previously explored. We have generated mice whose AMs show a deficient ability to sense oxygen after birth by deleting Vhl, a negative regulator of HIF transcription factors, in the CD11c compartment (CD11cΔVhl mice). VHL-deficient AMs show an immature-like phenotype and an impaired self-renewal capacity in vivo that persists upon culture ex vivo...
August 14, 2018: Cell Reports
Simone K Visser, Peter Bye, Lucy Morgan
Once neglected in research and underappreciated in practice, there is renewed interest in bronchiectasis unrelated to cystic fibrosis. Bronchiectasis is a chronic lung disease characterised by chronic cough, sputum production and recurrent pulmonary exacerbations. It is diagnosed radiologically on high resolution computed tomography chest scan by bronchial dilatation (wider than the accompanying artery). The causes of bronchiectasis are diverse and include previous respiratory tract infections, chronic obstructive pulmonary disease, asthma, immunodeficiency and connective tissue diseases...
August 20, 2018: Medical Journal of Australia
Fang-Yi Su, Selvi Srinivasan, Brian Lee, Jasmin Chen, Anthony J Convertine, T Eoin West, Daniel M Ratner, Shawn J Skerrett, Patrick S Stayton
Intracellular bacterial infections localized to the lung alveolar macrophage (AM) remain one of the most challenging settings for antimicrobial therapy. Current systemic antibiotic treatment fails to deliver sustained doses to intracellular bacterial reservoirs, which necessitates prolonged treatment regimens. Herein, we demonstrate a new intracellular enzyme-cleavable polymeric prodrug with tailored ciprofloxacin release profiles in the lungs and AM. The targeted polymeric prodrug, termed "drugamers", incorporates (1) hydrophilic mannose residues to solubilize the antibiotic cargo and to target and enhance AM uptake and intracellular delivery, and (2) enzyme-cleavable linkage chemistry to provide high and sustained intracellular AM drug dosing...
August 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
S J Klein, F Husain-Syed, C Karagiannidis, G F Lehner, K Singbartl, M Joannidis
Interactions between lung and kidney can significantly affect the course of acute diseases, a phenomenon that was first observed in the 1950s by describing pulmonary dysfunction in uremic patients. From animal experiments there is ample evidence for remote lung injury following acute kidney injury (AKI), with an increased risk for the development of pulmonary edema and acute respiratory distress syndrome (ARDS). Coincident ARDS and AKI are associated with higher rates of intubation and mechanical ventilation, significantly prolonged weaning from mechanical ventilation and increased mortality...
August 9, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Huan Tang, Sheng-Tao Yang, Da-Ming Ke, Yi-Fan Yang, Jia-Hui Liu, Xing Chen, Haifang Wang, Yuanfang Liu
Ag2 Se quantum dots (QDs) are novel fluorescent probes in the second near-infrared window with great imaging quality and biocompatibility. Surface modification is an essential step to disperse Ag2 Se QDs into biological fluids, and endow Ag2 Se QDs with diverse surface chemistry. However, the effect of surface chemistry on the biological behaviors and chemical fates of Ag2 Se QDs has not been studied, which hinders the design of suitable Ag2 Se QDs for biomedical applications. Here, the distribution, degradation, excretion and toxicity of 2-aminoethanethiol and mercaptopropionic acid coated Ag2 Se QDs (denoted as QDs-MEA and QDs-MPA, respectively) were systematically investigated in mice for a 28-day observation period after a single intravenous injection...
September 1, 2017: Toxicology Research
Cormac McCarthy, Elinor Lee, James P Bridges, Anthony Sallese, Takuji Suzuki, Jason C Woods, Brian J Bartholmai, Tisha Wang, Claudia Chalk, Brenna C Carey, Paritha Arumugam, Kenjiro Shima, Elizabeth J Tarling, Bruce C Trapnell
Pulmonary alveolar proteinosis (PAP) is a syndrome of reduced GM-CSF-dependent, macrophage-mediated surfactant clearance, dysfunctional foamy alveolar macrophages, alveolar surfactant accumulation, and hypoxemic respiratory failure for which the pathogenetic mechanism is unknown. Here, we examine the lipids accumulating in alveolar macrophages and surfactant to define the pathogenesis of PAP and evaluate a novel pharmacotherapeutic approach. In PAP patients, alveolar macrophages have a marked increase in cholesterol but only a minor increase in phospholipids, and pulmonary surfactant has an increase in the ratio of cholesterol to phospholipids...
August 7, 2018: Nature Communications
Hayley Loy, Denise I T Kuok, Kenrie P Y Hui, Miranda H L Choi, W Yuen, John M Nicholls, J S Malik Peiris, Michael C W Chan
Background: Highly pathogenic avian influenza viruses can cause severe forms of acute lung injury (ALI) in humans, where pulmonary flooding leads to respiratory failure. Therapeutic benefits of bone-marrow mesenchymal stromal cells (BM-MSCs) have been demonstrated in an influenza H5N1 ALI model. However, clinical translation is impractical and limited by declining efficacy with increase in donor age. Umbilical cord MSCs (UC-MSCs) are easier to obtain in comparison, and their primitive source may offer more potent therapeutic effects...
August 2, 2018: Journal of Infectious Diseases
Elin Boger, Oskar Wigström
The heterogeneous nature of the lung and the range of processes af-fecting pulmonary drug disposition make prediction of inhaled drugs chal-lenging. These predictions are critical, as the local exposure cannot be measured and current inhalation physiologically-based pharmacokinetic (PBPK) models do not capture all necessary features. Utilizing partial differential equations, we present an inhalation PBPK model to describe the heterogeneity in both lung physiology and particle size. The model mechanistically describes important processes such as deposition, mucocil-iary clearance and dissolution...
August 7, 2018: CPT: Pharmacometrics & Systems Pharmacology
Manolya Kukut Hatipoglu, Anthony J Hickey, Lucila Garcia-Contreras
For many years, administration of drugs by inhalation has been the mainstay treatment for obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease. Antibiotics and other drugs have been administered for decades as aerosols to treat other pulmonary disease in a clinical setting, but it was until the early 1980's that colistin was formally marketed as a solution for nebulization in Europe (Colomycin, Pharmax, Bexley). The solubility of other drugs and the size of the dose required to achieve therapeutic concentrations at the site of action, made treatment times long and difficult to be performed at home...
August 2, 2018: International Journal of Pharmaceutics
Christopher S King, A Whitney Brown, Shambhu Aryal, Kareem Ahmad, Scott Donaldson
Cystic fibrosis (CF) is a multi-organ, genetic disease resulting from dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). The primary clinical manifestations are bronchiectasis, chronic pulmonary infections with recurrent exacerbations, and pancreatic insufficiency. Advances in CF care have led to improved survival with over half of those affected being adults. As a result, adult pulmonary and critical care physicians will increasingly be involved in the care of these patients. Patients with CF are at risk for numerous conditions that require intensive care unit admission including respiratory failure, massive hemoptysis, pneumothorax, hepatic failure, and bowel obstruction...
August 2, 2018: Chest
Jeonghyun Park, Seonguk Kim, Hyungsun Lim, Airan Liu, Shuling Hu, JaeHoon Lee, Hanjing Zhuo, Qi Hao, Michael A Matthay, Jae-W Lee
BACKGROUND: We previously reported that microvesicles (MVs) released by human mesenchymal stem cells (MSC) were as effective as the cells themselves in both Escherichia coli lipopolysaccharide and live bacteria-induced acute lung injury (ALI) mice models. However, it remained unclear whether the biological effect of MSC MV can be applied to human ALI. METHODS: In the current study, we tested the therapeutic effects of MSC MVs in a well-established ex vivo perfused human model of bacterial pneumonia...
August 3, 2018: Thorax
Alexander J Kurdi, Benjamin A Voss, Tony H Tzeng, Steve L Scaife, Mouhanad M El-Othmani, Khaled J Saleh
Current literature regarding complications following total joint arthroplasty have primarily focused on patients with osteoarthritis (OA), with less emphasis on the trends and in-hospital outcomes of rheumatoid arthritis (RA) patients undergoing these procedures. The purpose of this study is to analyze the outcomes and trends of RA patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) compared to OA patients. Data from the Nationwide Inpatient Sample from 2006 to 2011 was extracted using the International Classification of Diseases, Ninth Revision codes for patients that received a TKA or THA...
July 2018: American Journal of Orthopedics
Magnus Paulsson, Karlhans F Che, Jonas Ahl, Johan Tham, Linda Sandblad, Margaretha E Smith, Ingemar Qvarfordt, Yu-Ching Su, Anders Lindén, Kristian Riesbeck
Pathogens causing pneumonia utilize the complement regulator vitronectin to evade complement-mediated killing. Although vitronectin is associated with several chronic lung diseases, the role of bronchoalveolar vitronectin in pneumonia has not been studied. This study sought to reveal the involvement of vitronectin in the bronchoalveolar space during pneumonia, to assess the effect of outer membrane vesicles and endotoxin on vitronectin release, and to determine whether bacterial pathogens utilize pulmonary vitronectin for evasion...
2018: Frontiers in Microbiology
Sílvia M Illamola, Hoa Q Huynh, Xiaoxi Liu, Zubin N Bhakta, Catherine M Sherwin, Theodore G Liou, Holly Carveth, David C Young
Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient's characteristics from adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations...
July 30, 2018: Antimicrobial Agents and Chemotherapy
Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Yasuhito Iseki, Shinji Matsutani, En Wang, Kosei Hirakawa, Masaichi Ohira
As a result of recent major advances in chemotherapy for metastatic colorectal cancer, the prognosis for patients with metastatic colorectal cancer has improved. However, elderly patients often cannot receive intensive therapy. There are still many problems to solve regarding treatment for elderly patients with metastatic colorectal cancer. We herein report a case of complete response of pulmonary metastases from rectal cancer to tegafur-uracil (UFT)/leucovorin (LV) + bevacizumab (Bmab) in an elderly patient...
May 2018: Case Reports in Oncology
Mikhail Kazachkov, Jose-Alberto Palma, Lucy Norcliffe-Kaufmann, Bat-El Bar-Aluma, Christy L Spalink, Erin P Barnes, Nancy E Amoroso, Stamatela M Balou, Shay Bess, Arun Chopra, Rany Condos, Ori Efrati, Kathryn Fitzgerald, David Fridman, Ronald M Goldenberg, Ayelet Goldhaber, David A Kaufman, Sanjeev V Kothare, Jeremiah Levine, Joseph Levy, Anthony S Lubinsky, Channa Maayan, Libia C Moy, Pedro J Rivera, Alcibiades J Rodriguez, Gil Sokol, Mark F Sloane, Tina Tan, Horacio Kaufmann
BACKGROUND: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia...
August 2018: Respiratory Medicine
Xuefei Cao, Yiying Wang, Rui Xiong, Levan Muskhelishvili, Kelly Davis, Patricia A Richter, Robert H Heflich
Many cigarette smoke-associated airway diseases involve alterations in mucin homeostasis. With the rationale that relevant tissue responses can be measured to evaluate the adverse health effects of tobacco products, we assessed changes in mucin secretion and the density and size of goblet cells in an in vitro human air-liquid-interface (ALI) airway tissue model after exposure to a tobacco smoke solution. Cultures were exposed daily for up to five consecutive days to a whole smoke solution (WSS) prepared by machine smoking Marlboro Red or Marlboro Silver cigarettes using the Canadian Intense (CI) protocol...
July 24, 2018: Toxicology
Tao-Tao Fu, Yun Zhao, Fei-Fei Yang, Han Wen, Chun-Yu Liu, Yong-Hong Liao
The pulmonary fate of inhaled poorly water-soluble drugs is not entirely clear. In this study, the main objective was to investigate the in vivo inhalation biopharmaceutics in the aspects of dissolution, mucociliary clearance, absorption and tissue binding using intratracheally administered budesonide and ciclesonide suspensions as model drugs. In doing so, this study first developed a method to differentiate between dissolved and undissolved ciclesonide in the lungs for evaluating in vivo dissolution. Following deposited in rat airways, the drug particles underwent rapid dissolution and mucociliary clearance, leading to the complete removal of drugs from the airways within 2 h and a limited absorption time less than 2 h...
July 23, 2018: International Journal of Pharmaceutics
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